Early cancer detection with sensitive and accurate biomarkers is a key to successful cancer treatment. Such biomarkers are especially important for cancers, which remain asymptomatic until disseminated stage, when curative response can rarely be achieved. Epithelial ovarian cancer (EOC) is a major health care problem as early detection with sufficient sensitivity and specificity is lacking. The 5-year survival rate for women diagnosed at the early stage is 90% whereas it is 20% if detected during late stage.
Human cancer antigen 125 (CA125), also known as mucin 16 or MUC16, is a complex transmembrane glycoprotein and the most widely used biomarker for EOC. It plays an important role not only in the diagnosis of primary epithelial ovarian cancer but also in the disease monitoring of postoperative women. The existing CA125 assays are double-determinant immunoassays based on detection of two different CA125 protein epitopes by two different monoclonal antibodies.
However, CA125 lacks sensitivity and cancer-specificity, especially at the early stages of EOC, owing to its elevated expression also in benign gynaecological conditions such as benign ovarian neoplasms and endometriosis, as well as in liver disease, and even during the normal ovulatory cycle. Therefore, CA125 is not recommended for screening of EOC.
During cancer progression, glycosylation patterns of many proteins change. Thus, detecting cancer related glycosylation patterns could offer novel diagnostic approaches for achieving improved specificity in tumor detection. Indeed, altered glycan composition has been reported in ovarian carcinoma compared to normal ovarian tissue, and further, altered glycan structures have been reported in serum CA125 of patients with EOC.
Chen et al. (J. Proteome Res., 2013, 12, 1408-1418) have reported that aberrant O-glycoforms of CA125 are present in serum from primary EOC patients and can be detected with a sandwich immunoassay using an O-glycan specific monoclonal antibody and VVL (Vicia Villosa lectin).
Although glycoprofiling of known tumor markers, such as CA125, and the use of a panel of different tumor markers seem to be promising for increasing the sensitivity and specificity of ovarian cancer detection through the elimination of many false positive results, there is still need for more specific markers which enable sufficient, easy-to-use discrimination between benign diseases and early, curable epithelial ovarian cancers.